6-24480067-T-C

Variant names:

• chr6-24480067-T-C
• rs6911965
• NM_001503.4:c.154-108A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001503.4(GPLD1):​c.154-108A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 701,976 control chromosomes in the GnomAD database, including 8,361 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.17 (2653 hom., cov: 32)
  • Exomes 𝑓: 0.14 (5708 hom.)
• Consequence: GPLD1 NM_001503.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.91
• Publications: 18 publications found

Genes affected

GPLD1 (HGNC:4459): (glycosylphosphatidylinositol specific phospholipase D1) Many proteins are tethered to the extracellular face of eukaryotic plasma membranes by a glycosylphosphatidylinositol (GPI) anchor. The GPI-anchor is a glycolipid found on many blood cells. The protein encoded by this gene is a GPI degrading enzyme. Glycosylphosphatidylinositol specific phospholipase D1 hydrolyzes the inositol phosphate linkage in proteins anchored by phosphatidylinositol glycans, thereby releasing the attached protein from the plasma membrane. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.273 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001503.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPLD1	NM_001503.4	MANE Select	c.154-108A>G		intron	N/A	NP_001494.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPLD1	ENST00000230036.2	TSL:1 MANE Select	c.154-108A>G		intron	N/A	ENSP00000230036.1	P80108-1
	GPLD1	ENST00000378243.8	TSL:1	n.214-108A>G		intron	N/A
	GPLD1	ENST00000891936.1		c.196-108A>G		intron	N/A	ENSP00000561995.1

Frequencies

GnomAD3 genomes AF: 0.171 AC: 25904 AN: 151758 Hom.: 2647 Cov.: 32

Gnomad AFR AF: 0.277

Gnomad AMI AF: 0.0373

Gnomad AMR AF: 0.151

Gnomad ASJ AF: 0.127

Gnomad EAS AF: 0.103

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.196

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.116

Gnomad OTH AF: 0.197

GnomAD4 exome AF: 0.136 AC: 74794 AN: 550100 Hom.: 5708 AF XY: 0.137 AC XY: 40610 AN XY: 295864

African (AFR) AF: 0.295 AC: 4631 AN: 15672

American (AMR) AF: 0.128 AC: 3890 AN: 30502

Ashkenazi Jewish (ASJ) AF: 0.131 AC: 2300 AN: 17614

East Asian (EAS) AF: 0.0835 AC: 2927 AN: 35052

South Asian (SAS) AF: 0.171 AC: 9590 AN: 55928

European-Finnish (FIN) AF: 0.193 AC: 7974 AN: 41404

Middle Eastern (MID) AF: 0.279 AC: 1073 AN: 3848

European-Non Finnish (NFE) AF: 0.118 AC: 37904 AN: 320336

Other (OTH) AF: 0.151 AC: 4505 AN: 29744

GnomAD4 genome AF: 0.171 AC: 25935 AN: 151876 Hom.: 2653 Cov.: 32 AF XY: 0.174 AC XY: 12899 AN XY: 74232

African (AFR) AF: 0.277 AC: 11458 AN: 41330

American (AMR) AF: 0.151 AC: 2304 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.127 AC: 439 AN: 3468

East Asian (EAS) AF: 0.104 AC: 535 AN: 5162

South Asian (SAS) AF: 0.155 AC: 748 AN: 4822

European-Finnish (FIN) AF: 0.196 AC: 2070 AN: 10544

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.116 AC: 7881 AN: 67966

Other (OTH) AF: 0.195 AC: 411 AN: 2108

Alfa AF: 0.133 Hom.: 6590

Bravo AF: 0.174

Asia WGS AF: 0.159 AC: 553 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.0060
DANN	Benign	0.67
PhyloP100		-2.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs6911965; hg19: chr6-24480295;